8th edition of the AJCC/TNM staging system of thyroid cancer: what to expect (ITCO#2)
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Endocrine-Related L Lamartina, G Grani et al. TNM staging of DTC 25:3 L7–L11
Cancer
RESEARCH LETTER
8th edition of the AJCC/TNM staging system of
thyroid cancer: what to expect (ITCO#2)
Dear Editor,
Differentiated thyroid cancer (DTC) has become one of cancer since 2013 (Lamartina et al. 2017). Cases included
the most frequently diagnosed malignancies, especially in our study met all the following criteria: (1) histological
among women and young adults (Davies & Welch 2014). diagnosis of thyroid cancer of follicular origin; (2) date
The outcomes are generally very good: disease recurrence of diagnosis between 1 January 2013 and 1 March 2017;
rates are low (Durante et al. 2013), and survival rates are (3) complete data on primary tumor pathology, including
excellent (Tuttle et al. 2017a). Evidence-based management minimal ETE, and initial treatment.
is crucial to avoid overtreatment of these low-risk tumors, The selected cohort analyzed included 1765 patients,
which can reduce quality of life and yet identify accurately 76% of whom were females. The median age at diagnosis
those requiring more aggressive therapy. Several staging was 48 years (range: 10–87). Total thyroidectomy
systems have been generated to inform DTC management. (or lobectomy + completion thyroidectomy) was
One of the most widely used is the tumor-node-metastasis performed in 1727 (98%) cases and followed by radioiodine
(TNM) classification elaborated by the American Joint remnant ablation in 954 (55%). Neck dissection was
Committee on Cancer (AJCC), which allows to predict the performed in 711 (40%) of the 1765 patients. Most of the
risk of cancer-related death. The 8th edition of the AJCC tumors (n = 1657, 94%) were papillary thyroid cancers;
staging system for thyroid cancer (AJCC-8) was recently the remaining 108 (6%) were follicular or Hürthle cell
published (Tuttle et al. 2017b) and is scheduled to be carcinomas. Estimated risks of recurrence calculated
implemented on 1 January 2018. Revision of the system according to the criteria recommended in 2015 by the
was undertaken to address several specific limitations American Thyroid Association were low in 1046 (59%),
identified in the 7th edition (AJCC-7), which has been in intermediate in 612 (35%) and high in 107 (6%) of the
use since 2009 (Tuttle et al. 2017a,b). The main changes cases. Microscopic ETE was found in 410 (23%), but only
(described in detail below and summarized in Table 1) 40 (2%) of these patients had gross invasion of the strap
are as follows: (1) an increase in the age threshold for muscles (sternohyoid, sternothyroid, thyroidhyoid and/or
defining high risk of thyroid cancer-related death and omohyoid muscles). Lymph node status for the 711
(2) a decrease in the unfavorable prognostic significance patients who underwent lymph node dissection was as
attributed to certain findings (i.e., cervical lymph node follows: pN0 (no metastasis) in 338 (19%); pN1a (central
metastases and microscopic extrathyroidal extension compartment metastases) in 221 (12%) and pN1b (lateral
(ETE), which has been re-defined to include only invasion compartment metastases) 152 (9%). Distant metastases
of the perithyroidal muscle). were found in 32 (1.8%) patients.
To assess the impact of transitioning to the new AJCC-8 As noted above, in the AJCC-8, the age threshold for
in terms of stage distribution and prevalence of each stage high risk of disease-specific mortality was raised from
class, we analyzed data extracted from the web-based 45 years – the median age at diagnosis in several published
database of the Italian Thyroid Cancer Observatory (ITCO) series – to 55 years (Nixon et al. 2016). This change
(www.itcofoundation.org), a network of thyroid cancer increases the proportion of relatively young patients
centers (including primary and tertiary centers) located whose mortality risk can be defined solely on the basis
throughout Italy. The database includes prospectively of the absence or presence of distant metastases (stages
updated, observational data provided by ITCO member I and II, respectively) (Table 1). As shown in Fig. 1A,
centers on patients consecutively diagnosed with thyroid the percentage of patients classified as ‘younger’ in our
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via free accessEndocrine-Related L Lamartina, G Grani et al. TNM staging of DTC 25:3 L8
Cancer
Table 1 AJCC TNM staging: 7th and 8th editions.
7th 8th
edition AgeEndocrine-Related L Lamartina, G Grani et al. TNM staging of DTC 25:3 L9
Cancer
Figure 1
DTC stage distributions in the ITCO cohort based
on the 7th and 8th editions of the AJCC system.
(A) The younger subcohorts defined by the
AJCC-7 and AJCC-8 comprised 698 patients aged
55 years, respectively. Restaging with
the AJCC-8 increased the percentages of patients
with stage I (from 56 to 64%) or II (from 8 to
31%) disease.
to stage III (Tuttle et al. 2017b), or regional metastases plus a far better agreement was found for the presence of gross
microscopic ETE (18/193, 9%). It should be noted that, ETE with invasion of perithyroidal muscles compared
differently from the AJCC-7, the ITCO database has always with invasion of perithyroidal fat only. The extensive
classified level VII lymph node metastases as central neck downstaging effect of the AJCC-8 was intentional: the
node lesions. This reflects the well-known difficulties in TNM staging system assesses the risk of DTC-related
distinguishing levels VI and VII and is consistent with death, which has proved to be very low for most patients.
the revised definitions adopted in the AJCC-8 (Tuttle Indeed, the results of retrospective cohort analyses
et al. 2017b). Since the same classification was also used confirm that the AJCC-8 provides more accurate estimates
for our AJCC-7 staging, some cases that met the criteria of DTC patients’ DSS (Kim et al. 2017a,b, Pontius et al.
for AJCC-7 stage IVa may have been erroneously reported 2017, Tuttle et al. 2017a). From a practical standpoint,
herein as stage III. As for the entire cohort, application application of the AJCC-8 criteria can be expected to
of the AJCC-8 criteria downstaged 477 (27%) of the 1765 simplify the staging process for most DTC patients, who
DTC patients. As a result, the estimated risk for 10-year will now be classified as ‘younger’. It will also markedly
disease-specific mortality was 40%) were restricted to risk (those with stages III–IV disease, where the DSS-10
2% (31/1765) of the patients who were 55 or older and isEndocrine-Related L Lamartina, G Grani et al. TNM staging of DTC 25:3 L10
Cancer
Graziano Ceresini13 16Dipartimento di Medicina Clinica e Sperimentale,
Rocco Bruno14 Università di Catania, Catania, Italy
Ruth Rossetto15 17Dipartimento di Scienze e Biotecnologie Medico-Chirurgiche,
Salvatore Tumino16 Università di Roma Sapienza, Latina, Italia
Marco Centanni17 18Unità Operativa Semplice Dipartimentale, Ospedale
Domenico Meringolo18 Bentivoglio, Ausl Bologna, Bologna, Italy
Maria Grazia Castagna19 19Dipartimento di Scienze Mediche, Chirurgiche
Domenico Salvatore20 e Neurologiche, Università di Siena, Siena, Italy
Antonio Nicolucci21 20Dipartimento di Medicina Clinica e Chirurgia, Università
Giuseppe Lucisano21 degli Studi di Napoli ‘Federico II’, Napoli, Italy
Sebastiano Filetti1 21Center for Outcomes Research and Clinical Epidemiology,
Cosimo Durante1 Pescara, Italy
1Dipartimento di Medicina Interna e Specialità Mediche, (Correspondence should be addressed to S Filetti:
Università di Roma Sapienza, Roma, Italy sebastiano.filetti@uniroma1.it)
2Dipartimento di Scienze Mediche, Università di Torino, *(L Lamartina and G Grani contributed equally to this
Torino, Italy work)
3Unità Operativa di Endocrinologia e Malattie del Ricambio,
Azienda Ospedaliera Universitaria di Ferrara, Ferrara, Italy
4Dipartimento di Medicina, Università di Perugia, Declaration of interest
The authors declare that there is no conflict of interest that could be
Perugia, Italy
perceived as prejudicing the impartiality of this article.
5Dipartimento di Scienze Mediche, Ospedale Casa Sollievo
della Sofferenza-IRCCS, San Giovanni Rotondo, Italy
6Cattedra di Chirurgia Endocrina, Area di Endocrinologia
Funding
e Malattie Metaboliche, Fondazione Policlinico Universitario This paper was funded by the Umberto Di Mario Foundation.
Agostino Gemelli, Università Cattolica del Sacro Cuore,
Roma, Italy
7Cattedra di Endocrinologia, Area di Endocrinologia
Author contribution statement
e Malattie Metaboliche, Fondazione Policlinico Universitario Livia Lamartina and Giorgio Grani: data management and interpretation,
analysis and writing. Antonio Nicolucci and Giuseppe Lucisano: statistical
Agostino Gemelli, Università Cattolica del Sacro Cuore,
analysis and data interpretation. Emanuela Arvat, Alice Nervo, Maria
Roma, Italy Chiara Zatelli, Roberta Rossi, Efisio Puxeddu, Silvia Morelli, Massimo
8Unità di Medicina Nucleare, Università di Roma Sapienza, Torlontano, Michela Massa, Rocco Bellantone, Alfredo Pontecorvi,
Teresa Montesano, Loredana Pagano, Lorenzo Daniele, Laura Fugazzola,
Roma, Italy
Graziano Ceresini, Rocco Bruno, Ruth Rossetto, Salvatore Tumino, Marco
9Unità di Endocrinologia, Dipartimento di Medicina
Centanni, Domenico Meringolo, Maria Grazia Castagna and Domenico
Traslazionale, Università del Piemonte Orientale, Salvatore: data collection and analysis, and manuscript editing. Cosimo
Durante and Sebastiano Filetti: concept, data interpretation, analysis and
Novara, Italy
manuscript editing.
10Unità di Patologia, Ospedale Mauriziano Umberto I di
Torino, Torino, Italy
11Divisione di Malattie Endocrine e Metaboliche, Istituto
Acknowledgements
Auxologico Italiano IRCCS, Milano, Italy G G and L L contributed to this paper as recipients of the PhD program of
12Dipartimento di Fisiopatologia Medico-Chirurgica e dei Biotechnologies and Clinical Medicine of the University of Rome, Sapienza.
Trapianti, Università degli Studi di Milano, Milano, Italy Medical editing services were provided by M E Kent and funded by the
Umberto Di Mario Foundation. The authors thank all the members of the
13Dipartimento di Medicina e Chirurgia, Università di Parma,
ITCO foundation: Ancona: Alessia Smerilli, Augusto Taccaliti. Bari: Vincenzo
Parma, Italy Triggiani, Giuseppina Renzulli. Brescia: Maria Beatrice Panarotto. Catania:
14Unità di Endocrinologia, Ospedale di Tinchi-Pisticci, Simona Quartararo, Dario Tumino. Ferrara: Ettore Degli Uberti. La Spezia:
Laura Camerieri, Mario Cappagli. Latina: Maria Giulia Santaguida.
Matera, Italy Livorno: Daniele Barbaro, Paola Lapi. Matera: Antonella Carbone. Milano:
15Divisione di Endocrinologia, Diabetologia e Metabolismo, Università degli Studi di Milano: Carla Colombo, Simone De Leo, Luca
Dipartimento di Scienze Mediche, Ospedale Molinette, A.O.U. Persani; Univesrità Humanitas di Milano: Andrea Lania. Napoli: Università
degli Studi di Napoli ‘Federico II’: Tommaso Porcelli. Istituto Nazionale
Città della Salute e della Scienza di Torino, Università di Tumori ITCCS ‘Fondazione G. Pascale’: Maria Grazia Chiofalo, Luciano
Torino, Torino, Italy Pezzullo. Novara: Gianluca Aimaretti, Chiara Mele. Padova: Caterina Mian,
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via free accessEndocrine-Related L Lamartina, G Grani et al. TNM staging of DTC 25:3 L11
Cancer
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Received in final form 24 November 2017
Accepted 29 November 2017
Accepted Preprint published online 30 November 2017
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